Advertisement

Chemistry and biological activity of alkaloids from the genus Schizanthus

  • Philippe ChristenEmail author
  • Sylvian Cretton
  • Munir Humam
  • Stefan Bieri
  • Orlando Muñoz
  • Pedro Joseph-Nathan
Article
  • 97 Downloads

Abstract

The genus Schizanthus (Solanaceae) comprises 12 accepted species primarily endemic to Chile. It is characterized by the presence of numerous tropane alkaloids found as ester derivatives of isomeric acids like angelic, senecioic, or tiglic, as well as mesaconic, itaconic, and citraconic acids, leading to numerous positional and configurational isomers. Up to now 50 alkaloids with these esters have been isolated and most of them are fully characterized. Analytical methods and techniques engaged during the investigation of this class of compounds, as well as their identification capabilities, are discussed. In several cases the absolute configuration is also well established, and some alkaloids are reported as biologically active. This review summarizes updated information on the distribution, botanical characteristics, phytochemical, and pharmacological knowledges of this genus up to mid-2018.

Keywords

Solanaceae Tropane ester derivatives Analysis Configurational and positional isomers Absolute configuration 

Abbreviations

AC

Absolute configuration

BA

6-Benzylaminopurine

CE

Capillary electrophoresis

COSY

Correlation spectroscopy

Da

Dalton

DFT

Density functional theory

ECD

Electronic circular dichroism

EI

Electron impact

FID

Flame ionization detector

FTIR

Fourier transform infrared

GC

Gas chromatography

HMBC

Heteronuclear multiple bond correlation

HPLC

High performance liquid chromatography

HPTLC

High performance thin-layer chromatography

HRESIMS

High-resolution electrospray ionization mass spectrometry

HSQC

Heteronuclear single-quantum correlation

IR

Infrared

ITMS

Ion trap mass spectrometry

IUPAC

International union of pure and applied chemistry

LLE

Liquid–liquid extraction

MEKC

Micellar electrokinetic chromatography

MS

Mass spectrometry

MW

Molecular weight

NACE

Non aqueous capillary electrophoresis

NOESY

Nuclear Overhauser effect spectroscopy

NMR

Nuclear magnetic resonance

PGC

Porous graphitic carbon

NAA

1-Naphthaleneacetic acid

NPD

Nitrogen phosphorus detector

SPE

Solid phase extraction

TDDFT

Time dependent density functional theory

TLC

Thin-layer chromatography

TOFMS

Time-of-flight mass spectrometry

UHPLC

Ultra-high performance liquid chromatography

UV

Ultraviolet

VCD

Vibrational circular dichroism

Notes

Acknowledgements

The authors want to thank Dr José San Martin, Departamento de Botanica, Universidad de Talca (Chile) for the identification of the plant material.

References

  1. Aehle E, Draeger B (2010) Tropane alkaloid analysis by chromatographic and electrophoretic techniques: an update. J Chromatogr B Anal Technol Biomed Life Sci 878:1391–1406.  https://doi.org/10.1016/j.jchromb.2010.03.007 CrossRefGoogle Scholar
  2. Afewerki S, Wang J-X, Liao W-W, Córdova A (2018) The chemical synthesis and applications of tropane alkaloids. The Alkaloids 81:1–84Google Scholar
  3. Bieri S, Muñoz O, Veuthey J-L, Christen P (2006a) Analysis of isomeric tropane alkaloids from Schizanthus grahamii by very fast gas chromatography. J Sep Sci 29:96–102.  https://doi.org/10.1002/jssc.200400008 CrossRefPubMedGoogle Scholar
  4. Bieri S, Varesio E, Muñoz O, Veuthey J-L, Christen P (2006b) Use of porous graphitic carbon column for the separation of natural isomeric tropane alkaloids by capillary LC and mass spectrometry. J Pharm Biomed Anal 40:545–551.  https://doi.org/10.1016/j.jpba.2005.07.007 CrossRefPubMedGoogle Scholar
  5. Bieri S, Varesio E, Muñoz O, Veuthey J-L, Tseng LH, Baumann U, Spraul M, Christen P (2006c) Identification of isomeric tropane alkaloids from Schizanthus grahamii by HPLC-NMR with loop storage and HPLC-UV-MS/SPE-NMR using a cryogenic flow probe. Phytochem Anal 17:78–86.  https://doi.org/10.1002/pca.889 CrossRefPubMedGoogle Scholar
  6. Burgueño-Tapia E, Joseph-Nathan P (2015) Vibrational circular dichroism: recent advances for the assignment of the absolute configuration of natural products. Nat Prod Commun 10:1785–1795PubMedGoogle Scholar
  7. Cerda-García-Rojas CM, Zepeda LG, Joseph-Nathan P (1990) A PC program for calculation of dihedral angles from proton NMR data. Tetrahedron Comput Methodol 3:113–118.  https://doi.org/10.1016/0898-5529(90)90113-M CrossRefGoogle Scholar
  8. Christen P (2000) Tropane alkaloids: old drugs used in modern medicine. Stud Nat Prod Chem 22:717–749CrossRefGoogle Scholar
  9. Christen P, Bieri S, Veuthey J-L (2008) Analysis of tropane alkaloids in biological matrices. In: Fattorusso E, Taglialatela-Scafati O (eds) Modern alkaloids: structure, isolation, synthesis and biology. Wiley-VCH Verlag GmbH & Co., Weinheim, p 665Google Scholar
  10. Christen P, Bieri S, Muñoz O (2009) Characterization of positional and configurational tropane alkaloid isomers by combining GC with NPD, MS and FTIR. Nat Prod Commun 4:1341–1348PubMedGoogle Scholar
  11. Christen P, Bieri S, Berkov S (2013) Methods of analysis: tropane alkaloids from plant origin. In: Ramawat KG, Mérillon JM (eds) Natural products. Springer, Berlin, pp 1009–1048CrossRefGoogle Scholar
  12. Cocucci AA (1989) El mecanismo floral de Schizanthus (Solanaceae). Kurtziana 20:113–132Google Scholar
  13. Cretton S, Glauser G, Humam M, Jeannerat D, Muñoz O, Maes L, Christen P, Hostettmann K (2010) Isomeric tropane alkaloids from the aerial parts of Schizanthus tricolor. J Nat Prod 73:844–847CrossRefGoogle Scholar
  14. Cretton S, Bartholomeusz TA, Humam M, Marcourt L, Allenbach Y, Jeannerat D, Muñoz O, Christen P (2011) Grahamines A-E, cyclobutane-centered tropane alkaloids from the aerial parts of Schizanthus grahamii. J Nat Prod 74:2388–2394.  https://doi.org/10.1021/np200450y CrossRefPubMedGoogle Scholar
  15. Cretton S, Muñoz O, Tapia J, Marcourt L, Maes L, Christen P (2017) Two new hygroline and tropane alkaloids isolated from Schizanthus hookeri and S. tricolor (Solanaceae). Nat Prod Commun 12:355–358PubMedGoogle Scholar
  16. De la Fuente G, Reina M, Muñoz O, San Martin A, Girault JP (1988) Tropane alkaloids from Schizanthus pinnatus. Heterocycles 27:1887–1897.  https://doi.org/10.3987/COM-88-4562 CrossRefGoogle Scholar
  17. Dembitsky VM (2008) Bioactive cyclobutane-containing alkaloids. J Nat Med 62:1–33CrossRefGoogle Scholar
  18. Dembitsky VM (2014) Naturally occurring bioactive cyclobutane-containing (CBC) alkaloids in fungi, fungal endophytes, and plants. Phytomedicine 21:1559–1581.  https://doi.org/10.1016/j.phymed.2014.07.005 CrossRefPubMedGoogle Scholar
  19. Draeger B (2002) Analysis of tropane and related alkaloids. J Chromatogr A 978:1–35.  https://doi.org/10.1016/S0021-9673(02)01387-0 CrossRefGoogle Scholar
  20. Eich E (2008) Solanaceae and Convolvulaceae: secondary metabolites. Springer, BerlinCrossRefGoogle Scholar
  21. Gambaro V, Labbe C, Castillo M (1982) Alkaloids from Schizanthus (Solanaceae). Bol Soc Chil Quim 27:296–298Google Scholar
  22. Gambaro V, Labbe C, Castillo M (1983) Angeloyl-, tigloyl-, and senecioyloxytropane alkaloids from Schizanthus hookeri. Phytochemistry 22:1838–1839.  https://doi.org/10.1016/s0031-9422(00)80289-7 CrossRefGoogle Scholar
  23. Grau J, Gronbach E (1984) Untersuchungen zur Variabilität in der Gattung Schizanthus (Solanaceae). Mitteilungen der Botanischen Staatssammlung München 20:111–203Google Scholar
  24. Griffin WJ, Lin GD (2000) Chemotaxonomy and geographical distribution of tropane alkaloids. Phytochemistry 53:623–637.  https://doi.org/10.1016/S0031-9422(99)00475-6 CrossRefPubMedGoogle Scholar
  25. Hartmann R, San-Martin A, Muñoz O, Breitmaier E (1990) Grahamine, an unusual tropane alkaloid from Schizanthus grahamii. Angew Chem 102:441–443CrossRefGoogle Scholar
  26. Humam M, Bieri S, Geiser L, Muñoz O, Veuthey JL, Christen P (2005) Separation of four isomeric tropane alkaloids from Schizanthus grahamii by non-aqueous capillary electrophoresis. Phytochem Anal 16:349–356.  https://doi.org/10.1002/pca.856 CrossRefPubMedGoogle Scholar
  27. Humam M, Muñoz O, Christen P, Hostettmann K (2007) Tropane alkaloids of the aerial parts of Schizanthus tricolor. Nat Prod Commun 2:743–747Google Scholar
  28. Humam M, Christen P, Muñoz O, Hostettmann K, Jeannerat D (2008) Absolute configuration of tropane alkaloids bearing two α, β-unsaturated ester functions using electronic CD spectroscopy: application to (R, R)-trans-3-hydroxysenecioyloxy-6-senecioyloxytropane. Chirality 20:20–25.  https://doi.org/10.1002/chir.20481 CrossRefPubMedGoogle Scholar
  29. Humam M, Kehrli T, Jeannerat D, Muñoz O, Hostettmann K, Christen P (2011a) Schizanthines N, O, and P, tropane alkaloids from the aerial parts of Schizanthus tricolor. J Nat Prod 74:50–53.  https://doi.org/10.1021/np1005423 CrossRefPubMedGoogle Scholar
  30. Humam M, Shoul T, Jeannerat D, Muñoz O, Christen P (2011b) Chirality and numbering of substituted tropane alkaloids. Molecules 16:7199–7209.  https://doi.org/10.3390/molecules16097199 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Hunziker AT (2001) Genera Solanacearum: the genera of Solanaceae illustrated, arranged according to a new system. A.R.G. Gantner, RuggelGoogle Scholar
  32. Jordan M, Humam M, Bieri S, Christen P, Poblete E, Muñoz O (2006) In vitro shoot and root organogenesis, plant regeneration and production of tropane alkaloids in some species of Schizanthus. Phytochemistry 67:570–578.  https://doi.org/10.1016/j.phytochem.2005.12.007 CrossRefPubMedGoogle Scholar
  33. Joseph-Nathan P, Gordillo-Román B (2015) Vibrational circular dichroism absolute configuration determination of natural products. Prog Chem Org Nat Prod 100:311–452.  https://doi.org/10.1007/978-3-319-05275-5_4 CrossRefPubMedGoogle Scholar
  34. Lounasmaa M, Tamminen T (1993) The tropane alkaloids. The Alkaloids 44:1–114Google Scholar
  35. Moore JM, Casale JF, Klein RF, Cooper DA, Lydon J (1994) Determination and in-depth chromatographic analyses of alkaloids in South American and greenhouse-cultivated coca leaves. J Chromatogr A 659:163–175CrossRefGoogle Scholar
  36. Morales MA, Ahumada F, Castillo E, Burgos R, Christen P, Bustos V, Muñoz O (2013) Inhibition of cholinergic contractions of rat ileum by tropane-type alkaloids present in Schizanthus hookeri. Z Naturforsch C 68:203–209CrossRefGoogle Scholar
  37. Muñoz O (1986) Alcaloides del tropano de Schizanthus pinnatus y de Schizanthus grahamii. Tesis, Universidad de La Laguna, SpainGoogle Scholar
  38. Muñoz O, Cortes S (1998) Tropane alkaloids from Schizanthus porrigens. Pharm Biol 36:162–166.  https://doi.org/10.1076/phbi.36.3.162.6341 CrossRefGoogle Scholar
  39. Muñoz MA, Joseph-Nathan P (2009) DFT-GIAO 1H and 13C NMR prediction of chemical shifts for the configurational assignment of 6β-hydroxyhyoscyamine diastereoisomers. Magn Reson Chem 47:578–584.  https://doi.org/10.1002/mrc.2432 CrossRefPubMedGoogle Scholar
  40. Muñoz MA, Joseph-Nathan P (2010) DFT-GIAO 1H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)-scopolamine and (−)-hyoscyamine. Magn Reson Chem 48:458–463.  https://doi.org/10.1002/mrc.2601 CrossRefPubMedGoogle Scholar
  41. Muñoz O, Hartmann R, Breitmaier E (1991) Schizanthine X, a new alkaloid from Schizanthus grahamii. J Nat Prod 54:1094–1096.  https://doi.org/10.1021/np50076a028 CrossRefGoogle Scholar
  42. Muñoz O, Schneider C, Breitmaier E (1994) A new pyrrolidine alkaloid from Schizanthus integrifolius. Liebigs Ann Chem 521–522.Google Scholar
  43. Muñoz O, Piovano M, Garbarino J, Hellwing V, Breitmaier E (1996) Tropane alkaloids from Schizanthus litoralis. Phytochemistry 43:709–713.  https://doi.org/10.1016/0031-9422(96)00308-1 CrossRefGoogle Scholar
  44. Muñoz MA, Muñoz O, Joseph-Nathan P (2006) Absolute Configuration of natural diastereoisomers of 6β-hydroxyhyoscyamine by vibrational circular dichroism. J Nat Prod 69:1335–1340.  https://doi.org/10.1021/np060133j CrossRefPubMedGoogle Scholar
  45. Muñoz MA, Muñoz O, Joseph-Nathan P (2010) Absolute configuration determination and conformational analysis of (−)-(3S,6S)-3α,6β-diacetoxytropane using vibrational circular dichroism and DFT techniques. Chirality 22:234–241.  https://doi.org/10.1002/chir.20734 CrossRefPubMedGoogle Scholar
  46. Muñoz MA, Martinez M, Joseph-Nathan P (2012) Absolute configuration and stereochemical analysis of 3α,6β-dibenzoyloxytropane. Phytochem Lett 5:450–454.  https://doi.org/10.1016/j.phytol.2012.04.003 CrossRefGoogle Scholar
  47. Muñoz MA, Arriagada S, Joseph-Nathan P (2014) Chiral resolution and absolute configuration of 3α,6β-dicinnamoyloxytropane and 3α,6β-di(1-ethyl-1H-pyrrol-2-ylcarbonyloxy)tropane, constituents of Erythroxylum species. Nat Prod Commun 9:27–30PubMedGoogle Scholar
  48. Muñoz MA, Gonzalez N, Joseph-Nathan P (2016) Enantiomeric high-performance liquid chromatography resolution and absolute configuration of 6β-benzoyloxy-3α-tropanol. J Sep Sci 39:2720–2727.  https://doi.org/10.1002/jssc.201600061 CrossRefPubMedGoogle Scholar
  49. Muñoz-Schick M, Moreira-Muñoz A (2008) El género Schizanthus (Solanaceae) en Chile. Revista Chagual 6:21–32Google Scholar
  50. Oksman-Caldentey KM, Arroo R (2000) Regulation of tropane alkaloid metabolism in plants and plant cell cultures. In: Verpoorte R, Alfermann A (eds) Metabolic engineering of plant secondary metabolism. Kluwer Academic Publishers, Dordrecht, pp 253–281CrossRefGoogle Scholar
  51. Peña RC, Muñoz O (2002) Cladistic relationships in the genus Schizanthus (Solanaceae). Biochem Syst Ecol 30:45–53.  https://doi.org/10.1016/s0305-1978(01)00063-1 CrossRefGoogle Scholar
  52. Pérez F (2011) Discordant patterns of morphological and genetic divergence in the closely related species Schizanthus hookeri and S. grahamii (Solanaceae). Plant Syst Evol 293:197–205.  https://doi.org/10.1007/s00606-011-0433-3 CrossRefGoogle Scholar
  53. Pérez F, Arroyo MTK, Medel R, Hershkovitz MA (2006) Ancestral reconstruction of flower morphology and pollination systems in Schizanthus (Solanaceae). Am J Bot 93:1029–1038CrossRefGoogle Scholar
  54. Pérez F, Spencer P, Cienfuegos A, Suarez L (2011) Microsatellite markers for the high Andean species Schizanthus hookeri and S. grahamii (Solanaceae). Am J Bot 98:e114–e116.  https://doi.org/10.3732/ajb.1000487 CrossRefPubMedGoogle Scholar
  55. Rahman A, Khattak KF, Nighat F, Shabbir M, Hemalal KD, Tillekeratne LM (1998) Dimeric tropane alkaloids from Erythroxylum moonii. Phytochemistry 48:377–383.  https://doi.org/10.1016/S0031-9422(97)01079-0 CrossRefGoogle Scholar
  56. Reich E, Schibli A (2006) High-performance thin-layer chromatography for the analysis of medicinal plants. Thieme, New YorkGoogle Scholar
  57. Reina M, Burgueño-Tapia E, Bucio MA, Joseph-Nathan P (2010) Absolute configuration of tropane alkaloids from Schizanthus species by vibrational circular dichroism. Phytochemistry 71:810–815.  https://doi.org/10.1016/j.phytochem.2010.02.004 CrossRefPubMedGoogle Scholar
  58. Ripperger H (1979) Schizanthine A and B, two new tropane alkaloids from Schizanthus pinnatus. Phytochemistry 18:171–173CrossRefGoogle Scholar
  59. Ruiz H, Pavón J (1794) Florae Peruvianae, et Chilensis Prodromus I. Devoti, RomeGoogle Scholar
  60. San Martin A, Rovirosa J, Gambaro V, Castillo M (1980) Tropane alkaloids from Schizanthus hookeri. Phytochemistry 19:2007–2008.  https://doi.org/10.1016/0031-9422(80)83023-8 CrossRefGoogle Scholar
  61. San Martin A, Labbe C, Muñoz O, Castillo M, Reina M, De la Fuente G, Gonzalez A (1987) Tropane alkaloids from Schizanthus grahamii. Phytochemistry 26:819–822.  https://doi.org/10.1016/S0031-9422(00)84794-9 CrossRefGoogle Scholar
  62. Sergeiko A, Poroikov VV, Hanus LO, Dembitsky VM (2008) Cyclobutane-containing alkaloids: origin, synthesis, and biological activities. Open Med Chem J 2:26–37.  https://doi.org/10.2174/1874104500802010026 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Sudzuki F (1969) Tesis Ingeniero Agrónomo. SantiagoGoogle Scholar
  64. ThePlantList (2013) http://www.theplantlist.org. Accessed 31 Aug 2018
  65. Walter D (1969) A revision of the genus Schizanthus (Solanaceae). Indiana UniversityGoogle Scholar
  66. Zepeda LG, Burgueño-Tapia E, Joseph-Nathan P (2011) Myrtenal, a controversial molecule for the proper application of the CIP sequence rule for multiple bonds. Nat Prod Commun 6:429–432PubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.School of Pharmaceutical SciencesUniversity of Geneva, University of LausanneGeneva 4Switzerland
  2. 2.Departamento de Química, Facultad de CienciasUniversidad de ChileSantiagoChile
  3. 3.Departamento de QuímicaCentro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico CityMexico

Personalised recommendations